NIEMANN-PICK DISEASE TYPE A: MOLECULAR ANALYSIS OF NEURONAL MEMBRANE LIPID AND PROTEIN COMPOSITION, TRAFFICKING, AND FUNCTION

The Niemann Pick disease Type A is an inherited deficiency in the Acid Sphingomyelinase gene (ASM) that causes mental retardation and early death. ASM plays a crucial role in the metabolism of Sphingomyelin, an essential lipid in neuronal development that contributes to the maturation of the axonal membrane. Using an animal model that mimic the human disease we will study the molecular basis of the disorder, both in vitro and in vivo, and how it affects neuronal circuitry and functionality. Moreover, we will try rescue experiments of the enzymatic activity that could help in the establishment of a therapy. Understanding how lipid metabolism is involved in the development and maturation of the central nervous system represents the first step to improve quality of life or even cure the increasing number of patients suffering neurological disorders that in most of the cases imply long-term degenerative pathologies with elevated sociological and economical costs.